Surgical Pathology Unknown Conference:
Case # 1: A 68 year old man presented with hematuria. Upon cystoscopy, a 5
cm ulcerated mass was found. A transurethral resection (TUR) was performed.
Diagnosis:
1- Invasive High Grade Urothelial Carcinoma.
2- Small Cell Carcinoma.
3- Secondary Extension of Prostatic Adenocarcinoma .
4- Paraganglioma.
Histology: The infitrative lesion is well vascularized showing a vaguely nested
appearance. It is composed of large round to polygonal cells with abundant
amphophilic granular cytoplasm and modest degree of nuclear pleomorphism.
Mitotic figures are lacking. Necrosis was not present. Immunostains reveal
positive reactivity for chromogranin and synaptophysin. Focal S100 reactivity was
seen. Cytokeratin AE1/AE3 stains were negative.
Discussion: Paragagliomas of the urinary bladder are rare tumors that can be
misdiagnosed as urothelial carcinoma due to their infiltrative nature, occasionally
diffuse architecture and confounding cautery artifact encountered on TUR.
Rarely, the lesion is clinically suspected either due to associated symptoms such
as hypertension, episodic palpitation/headache on micturition or due to lack of a
typical cystscopic appearance of urothelial carcinoma. Making such a distinction
is of great importance given the potential differences in prognosis and
management between paraganglioma and muscle invasive high grade urothelial
carcinoma. Morphologic features such as the presence of focal more typical
Zellballen pattern and rich fibrovascular network and the lack of desmoplastic
reaction accompanying muscularis propria invasion should raise the possibility of
paraganglioma. Immunostains for neuroendocrine markers , S100 (sustentacular
pattern) and cytokeratins (-) can help establish the diagnosis.
In general, several syndromes have been found to be associated with the risk of
development of pheochromocytomas/paragangliomas. These include: multiple
endocrine neoplasia type 2 (MEN 2, susceptibility gene: RET), von Hippel-Lindau
disease (VHL, susceptibility gene: VHL), neurofibromatosis 1 (NF 1), and
paraganglioma syndromes type 1, 3, and 4 (susceptibility genes: succinate
dehydrogenase gene, SDH, subunits D, C and B, respectively).
Reference:
Zhou M, Epstein JI, Young RH. Paraganglioma of the urinary bladder: a lesion
that may be misdiagnosed as urothelial carcinoma in transurethral resection
specimens. Am J Surg Pathol. 2004 Jan;28(1):94-100.
Pawlu C, Bausch B, Reisch N, Neumann HP. Genetic testing for
pheochromocytoma-associated syndromes. Ann Endocrinol (Paris). 2005
Jun;66(3):178-85.
Case # 2: A 36 year old man underwent a radical nephrectomy for a 32 cm renal
mass. On imaging studies, the tumor extended to the retropertineum with
secondary metastasis to liver and lung.
Diagnosis:
1- Renal Cell Carcinoma with Sarcomatoid Features.
2- Urothelial Carcinoma with Sarcomatoid Features.
3- Dedifferentiated Liposarcoma.
4- Malignant Solitary Fibrous Tumor.
Histology: On Low power examination, the relatively well circumscribed tumor
demonstrates variable degree of cellularity. Areas of geographic necrosis are
easily found. Less cellular areas are composed of relatively bland spindle cells
separated by parallel bands of thick collagen featuring a “hemangiopercytoma”
like vascular pattern. The densely cellular areas show plump, epithelioid, spindle
cells with markedly increased mitotic activity and necrosis. The tumor only focally
invaded the renal parenchyma. On immunostains, the tumor cells were positive
for CD34 and negative for Actin, CD99, EMA, AE1/AE3, CAM 5.2 and S100.
Discussion: Solitary fibrous tumors (SFT) have been reported to rarely
originates in renal parenchyma, renal capsule and renal pelvis. Although the
current example demonstrated frank histologic features consistent with its
clinically mailgnant behavior, other renal SFT’s lacking increased cellularity,
pleomorphism, mitotic activity and necrosis are expected to behave in a benign
fashion. Therefore, distinguishing an SFT from the more common sarcomatoid
renal cell carcinoma is crucially important. The differential of a renal spindle cell
tumor should also include monophasic angiomyolipoma, leiomyosarcoma and
the rare synovial sarcoma. Immunostains are helpful in confirming a histologic
impression of SFT by demonstrating its typical
CD34 (+), Bcl2 (+) and SMA (-) phenotype.
References:
Wang J, Weiss LM, Hu B, Chu P, Zuppan C, Felix D, Rausei-Mills V, Chase DR.
Usefulness of immunohistochemistry in delineating renal spindle cell tumours. A
retrospective study of 31 cases. Histopathology. 2004 May;44(5):462-71.
Wang J, Arber DA, Frankel K, Weiss LM. Large solitary fibrous tumor of the
kidney: report of two cases and review of the literature.
Am J Surg Pathol. 2001 Sep;25(9):1194-9.
Case # 3: A 16 year old male presented with a left testicular mass. A partial
orchiectomy was performed.
Diagnosis:
1- Endodermal Sinus Tumor.
2- Fibrous Pseudotumor.
3- Mesothelioma.
4- Adenomatoid Tumor.
Histology: The 1.8 cm lesion is primarily composed of a dense fibrous tissue
with a relatively more cellular central area composed of stellate to spindle cells
with features of myofibrobalsts. Vascular structures lined by plump endothelial
cells without significant cytologic atypia are present. A modest mixed
inflammatory infiltrate is associated, The well circumscribed lesion originates in
the tunica albuginea. Underlying testicular parenchyma is spared. No evidence of
intratubular germ cell neoplasia is seen.
Discussion: Fibrous pseudotumors and proliferative funniculitis (inflammatory
pseudotumors) are considered by many as part of a spectrum of non-neoplastic
fibroblastic/myofibroblastic proliferations that affects the tunica and paratesticular
region. Some examples may demonstrate a pseudosacromatous morphology .
Others are almost completely fibrotic and collagenized with associated
calcifications. Fibrous pseudotumors can present as multiple nodules and at
times as free-lying scrotal masses (corpora libra). They are usually associated
with a history of hydrocele or prior trauma or infection. Fibrous and inflammatory
pseudotumors are to be distinguished from “fibroma of tunica albuginea” that can
carry some morphologic and immunohistochemical (CD34 positivity)
resemblance to solitary fibrous tumors of other site.
References:
Begin LR, Frail D, Brzezinski A. Myofibroblastoma of the tunica testis: evolving
phase of so-called fibrous pseudotumor? Hum Pathol. 1990 Aug;21(8):866-8.
Jones MA, Young RH, Scully RE. Benign fibromatous tumors of the testis and
paratesticular region: a report of 9 cases with a proposed classification of
fibromatous tumors and tumor-like lesions. Am J Surg Pathol. 1997
Mar;21(3):296-305.
Case # 4: A 60 year old underwent a radical nephrectomy for two separate renal
masses each measuring 3 cm in largest diameter. Both tumors shared similar
morphologic features.
Diagnosis:
1- Epithelioid Angiomyolipoma.
2- Oncocytoma.
3- Hybrid Oncocytic Neoplasm with Oncocytoma and Chromophobe Renal Cell
Carcinoma Components.
4- Medullary Carcinoma of Kidney.
Histology: Both tumors were composed of an oncocytic epithelial proliferation
arranged in solid islands and nests. Focal hyalinized - edematous stroma
separating the epithelial islands is seen as characteristically found in renal
oncocytomas. In the latter areas, the epithelial cells contain typical round variable
sized nuclei with one or more small nucleoli. In other areas, cytologic features of
chromophobe cell carcinoma are demonstrated to include the presence of
“raisinoid” nuclear morphology imparted by the irregular nuclear membranes and
the existence of a vague perinuclear halo. Mitotic figures are absent. Oncocytosis
was not present in the submitted non neoplastic kidney.
Discussion: Hybrid oncocytic renal neoplasms may be encountered in the
setting of Birt-Hogg-Dube (BHD) syndrome. BHD is an autosomal dominant
genodermatosis
characterized by the development of benign hair follicle tumors
(fibrofolliculomas), an increased risk of renal neoplasia and spontaneous
pneumothorax. BHD patients can develop multiple, at time bilateral renal tumors
with variable morphology to include hybrid oncocytic neoplasms , chromophobe
renal cell carcinomas and conventional clear cell carcinomas. In most patients,
the non neoplastic renal parenchyma reveals microscopic evidence of
“oncocytoisis”.
The BHD gene is mapped to chromosome 17p11.2. It encodes a novel protein of
yet unknown function (follicullin). Relatives of affected individual can be tested for
the presence of a germline BHD mutation to determine if they are at increased
risk to develop renal malignancies.
References:
Pavlovich CP, Grubb RL 3rd, Hurley K, Glenn GM, Toro J, Schmidt LS,
Torres-Cabala C, Merino MJ, Zbar B, Choyke P, Walther MM, Linehan WM.
Evaluation and management of renal tumors in the Birt-Hogg-Dube syndrome. J
Urol. 2005 May;173(5):1482-6.
Pavlovich CP, Walther MM, Eyler RA, Hewitt SM, Zbar B, Linehan WM, Merino
MJ. Renal tumors in the Birt-Hogg-Dube syndrome. Am J Surg Pathol. 2002
Dec;26(12):1542-52.
Case # 5: A 42 year old male underwent a circumcision after a long history of
phimosis.
Diagnosis:
1.
2.
3.
4.
Squamous Intraepithelial Lesion, Low Grade.
Warthy Squamous Intraepithelial Lesion (WSIL), High Grade.
Ballanitis Circumscripta Plasmacellularis (Zoon Balanitis).
Balanitis Xerotica Obliterans (Lichen Sclerosis et Atrophicus).
Histology: The epidermis demonstrates focal marked hyperkeratosis and
acanthosis. Hydropic degeneration is focally present in the basal layer imparting
a vacuolar change at the DE junction. The superficial portion of the lamina
propria shows marked edema and homogenization of collagen. A mixed dermal
inflammatory infiltrate is seen. There is no evidence of squamous dysplasia.
Discussion: Balanatis Xerotica Obliterans (BXO) is a frequent finding in
specimens obtained for phimosis. Although the relationship of BXO to carcinoma
is not entirely clear, BXO lesions can be found in 30-70% of penile squamous
carcinoma resections. The association seems to be stronger with special types of
carcinoma such as papillary and verrucous penile carcinoma. Dysplastic or CIS
changes can rarely be seen in the epidermis of hyperplastic BXO.
References:
Velazquez EF, Cubilla AL. Lichen sclerosus in 68 patients with squamous cell
carcinoma of the penis: frequent atypias and correlation with special carcinoma
variants suggests a precancerous role. Am J Surg Pathol. 2003
Nov;27(11):1448-53.
Case # 6: A 59 year old female presented with hematuria. A cystoscopy and
transurethral resection was performed.
Diagnosis:
1.
2.
3.
4.
Diffuse Large B Cell Lymphoma.
Small Cell Carcinoma.
Lymphoepithelioma Like Carcinoma (LELC) of Urinary Bladder.
Severe Chronic Follicular Cystitis.
Histology: The epithelial neoplasm is composed of a proliferation of
undifferentiated highly atypical cells arranged in a syncitial pattern with indistinct
cytoplasmic borders. Characteristic of LELC, the epithelial cells contain large
vesicular nuclei with very prominent nucleoli. The latter is associated with a
dense obscuring lymphoid infiltrate. The lymphoid cells are smaller in size.
Mitotic figures are easily identified. The tumor extensively invades the
muscularis propria. The surface urothelium show no evidence of flat carcinoma
in situ (CIS).
Discussion: LELC is a rare type of urinary bladder carcinoma. The associated
dense lymphoid host response could lead to a misdiagnosis of such lesions as
malignant lymphoma especially on small TUR biopsies with extensive cautery
artifact. Immunostains for cytokeratins AE1/AE3, CK7 and EMA could be of help
in such cases. The lymphoid infiltrate is usually composed of a mixture of B and
T cells. Unlike their nasopharyngeal counterparts, EBV studies for LMP1 and
EBER have been shown to be negative in LELC of bladder. Distinguishing
bladder tumors with pure or predominant LELC morphology from other
undifferentiated and high grade urothelial carcinoma may have implications on
patient management given the relatively higher chemotherapy response rates
and the potentials for bladder salvage.
References:
Lopez-Beltran A, Luque RJ, Vicioso L, Anglada F, Requena MJ, Quintero A,
Montironi R. Lymphoepithelioma-like carcinoma of the urinary bladder: a
clinicopathologic study of 13 cases. Virchows Arch. 2001 Jun;438(6):552-7.
Amin MB, Ro JY, Lee KM, Ordonez NG, Dinney CP, Gulley ML, Ayala AG.
Lymphoepithelioma-like carcinoma of the urinary bladder. Am J Surg Pathol.
1994 May;18(5):466-73.